Abstract for RACB82083

Dibromochloropropane: Reproduction and Fertility Assessment in CD-1 Mice When Administered by Gavage

Abstract

The following abstract presents results of a study conducted by a contract laboratory for the National Toxicology Program. The findings were not evaluated in accordance with the levels of evidence for reproductive or developmental criteria established by NTP in March 2009. The findings and conclusions for this study should not be construed to represent the views of NTP or the U.S. Government.

Dibromochloropropane (DBCP), a pesticide that was widely used, and still contaminates groundwater supplies in agricultural areas, was tested because of the known toxicity in rats and relative paucity of data in mice. DBCP was an early RACB study using Swiss CD-1 mice. Data on food and water consumption's, body weights, and clinical signs during a two week dose-range-finding study (Task 1) were used to set exposure concentrations for the Task 2 continuous cohabitation study at 25.0, 50.0, and 100.0 mg/kg by gavage in corn oil.

In the F0 animals, 4 females, 2 females, 2 females, and 3 females and a male died in the control through high dose groups, respectively. The deaths were not attributed to DBCP exposure.

In the low and high dose groups, there was a 10% and 8%, respectively, decrease in the number of litters/pair. However, there was no change in the number of pups/litter, pup viability, or pup weight adjusted for litter size. There were no treatment-related reductions in F0 mouse body weight.

In the absence of a change in pup parameters, no Task 3 was conducted, and the control and high dose mice were reared for second generation evaluation. Body weights between mice in these two groups were not different at weaning or at cohabitation. In the Task 4 F1 mating trial, controls and high dose DBCP mice delivered the same number of litters/group, pups/litter, and proportion viable pups; adjusted pup body weight was not affected by DBCP.

After the F2 litters were delivered and evaluated, the F1 adults were killed and necropsied. In the high dose treated males, there was a 16% increase in relative liver weight, and a decrease of 8% and 20% in relative epididymis and prostate weights, respectively. There were no differences between the groups in sperm endpoints. DBCP treatment increased female relative liver weight by 6%; vaginal cytology was not performed.

This study found that DBCP produced minor effects (fewer litters/F0 pair, and reduced epididymis and prostate weights in F1 mice) concomitant with minor increases in liver weight and no change in body weight. These changes are relatively small, compared to effects seen in rats, and probably represent a significant species difference in response.